NEURAL SUBSTRATES OF AGE-RELATED COGNTIVE DECLINE IN MONKEYS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。(From父母波士顿大学的老龄化PPG <$仅在NEPRC进行的纵向研究）恒河猴是正常人类衰老的模型，其使得认知测试之后能够最佳地保存脑组织以用于多学科研究。拟议的研究验证了一个假设，即年龄相关的认知能力下降是由一系列轻度退行性变化引起的，这些变化始于白色物质的炎症，随后是神经元的功能变化和结构变化。我们将研究三组猴子。第一组36人将用于一项横断面研究，受试者的年龄范围为5 - 30岁。在行为测试之后，MRI扫描之后将进行体内神经生理学和两阶段灌注，以提供新鲜和固定的组织，以识别认知下降的大脑变化。第二个队列的6只中年猴将与队列1一样进行，不同之处在于它们将被固定用于电子显微镜检查，以补充现有样本，并允许识别与认知下降相关的首次出现在中年的超微结构变化。第三组12只中年早期猴（年龄13-15岁）将纵向随访4年以上，进行重复行为测试、脑部MRI扫描以及血液和CSF样本。由于认知障碍的患病率在13 - 15岁时较低，但在20岁时较高，这些数据将使我们能够确定个体猴子的认知特征和下降速度。纵向MRI将揭示脑形态学的同时变化，CSF和血液样本将允许评估生物标志物。对于队列1和3，在固定大脑其余部分之前，将立即对复合动作电位进行体内神经生理学评估，然后从一个半球采集未固定的样本。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. (From parent Aging PPG at Boston University ¿ Longitudinal Study only conducted at NEPRC) The rhesus monkey is a model of normal human aging that enables cognitive testing to be followed by optimal preservation of brain tissue for multidisciplinary studies. The proposed studies test the hypothesis that age-related cognitive decline results from a cascade of mild degenerative changes beginning with inflammation in white matter followed by functional and then structural changes in neurons. We will study three cohorts of monkeys. The first cohort of 36 will be used in a cross-sectional study and will consist of subjects covering the adult life span from 5 to 30 years old. After behavioral testing, MRI scans will be followed by in vivo neurophysiology and a two stage perfusion to provide fresh and fixed tissue to identify brain changes underlying cognitive decline. A second cohort of 6 middle aged monkeys will proceed like cohort 1 except they will be fixed for electron microscopy to supplement existing samples and allow identification of the ultrastructural changes that appear first in middle age in relation to cognitive decline. A third cohort of 12 early middle aged monkeys (ages 13-15) will be followed longitudinally for 4+ years with repeated behavioral testing, MRI scans of the brain, and samples of blood and CSF. As the prevalence of cognitive impairment is low at 13 - 15 but high by 20, these data will allow us to identify the cognitive profile and rate of decline of individual monkeys. Longitudinal MRIs will reveal concurrent changes in brain morphology, and CSF and blood samples will allow biomarkers to be assessed. For cohorts 1 and 3, in vivo neurophysiological assessment of compound action potentials will be followed immediately by collection of unfixed samples from one hemisphere before the remainder of the brain is fixed.